This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This proposal describes the molecular and phenotypic characterization of B cell differentiation and perturbations of the process in leukemogenesis. We will use a combination of gene expression, molecular and multi-parameter flow cytometry (FACS) studies to reveal further details of fetal vs. adult B cell development and to investigate the mechanisms that are responsible for the switch from fetal to adult hematopoietic development in the mouse. We will use FACS to study the changes in B cell development in neonatal and adult mice and to study intracellular signaling pathways in the B-1 and B-2 B cell progenitors. Furthermore, we will also use FACS to sort B-1 and B-2 progenitors for gene expression studies. The study of the hematopoeitic developmental switch will have great implication in understanding the development and treatment in human diseases and cancers. We will also establish a new methodology, which combines FACS and fluorescence in situ hybridization (FISH), for cancer diagnosis, prognostication, and evaluating drug efficacy using B-CLL or multiple myeloma as a model system. This research is designed to study the differences between fetal (B-1) and adult B (B-2) cell development and to find the genetic switch that switches fetal B cell development to adult B cell development. Each of the B cell development is important because they participate in distinct aspect of immune response. This research will also establish a new method for cancer detection that is more rapid and more efficient.